Sp-1 Binds Promoter Elements That Are Regulated by Retinoblastoma and Regulate CTP:Phosphocholine Cytidylyltransferase-α Transcription

The retinoblastoma (Rb) protein is implicated in transcriptional regulation of at least five cellular genes. Co-transfection of Rb and truncated promoter constructs has defined a discrete element (retinoblastoma control element (RCE)) within the promoters of each of these genes as being necessary for Rb-mediated transcriptional control. In the present report we demonstrate that two RCEs identified within the CTP:phosphocholine cytidylyltransferase-α (CTα) proximal promoter are essential to promote transcription. Mutations that abolished each RCE markedly decreased CTα transcription. Co-transfection of Rb and truncated promoter constructs demonstrated that Rb regulates CTα expression by different mechanisms depending on the phase of the cell cycle. The regulation of CTα expression by Rb required both the Sp1 and the RCEs. Maximal expression occurred when both Rb and Sp1 were overexpressed. Moreover, RCEs were required for Rb association with the DNA. This regulatory mechanism alters CTα activity and thereafter changes PC availability and cell physiology. This is the first report demonstrating not only that surrounding Sp1 binding sites alter regulation mediated by Rb, but also that the expression of a gene involved in PC biosynthesis shares a common regulatory pathway with genes responsible for cell growth and differentiation. The retinoblastoma (Rb) protein is implicated in transcriptional regulation of at least five cellular genes. Co-transfection of Rb and truncated promoter constructs has defined a discrete element (retinoblastoma control element (RCE)) within the promoters of each of these genes as being necessary for Rb-mediated transcriptional control. In the present report we demonstrate that two RCEs identified within the CTP:phosphocholine cytidylyltransferase-α (CTα) proximal promoter are essential to promote transcription. Mutations that abolished each RCE markedly decreased CTα transcription. Co-transfection of Rb and truncated promoter constructs demonstrated that Rb regulates CTα expression by different mechanisms depending on the phase of the cell cycle. The regulation of CTα expression by Rb required both the Sp1 and the RCEs. Maximal expression occurred when both Rb and Sp1 were overexpressed. Moreover, RCEs were required for Rb association with the DNA. This regulatory mechanism alters CTα activity and thereafter changes PC availability and cell physiology. This is the first report demonstrating not only that surrounding Sp1 binding sites alter regulation mediated by Rb, but also that the expression of a gene involved in PC biosynthesis shares a common regulatory pathway with genes responsible for cell growth and differentiation. Phosphatidylcholine (PC) 3The abbreviations used are: PC, phosphatidylcholine; CT; CTP:phosphocholine cytidylyltransferase; FBS, fetal bovine serum; LUC, luciferase; Rb, retinoblastoma protein; RCE, retinoblastoma control element; RCP, retinoblastoma control protein; qPCR, quantitative PCR; CMV, cytomegalovirus; ChIP, chromatin immunoprecipitation. is the major phospholipid in mammalian cells and is a precursor for the synthesis of sphingomyelin and phosphatidylserine. PC biosynthesis occurs in all nucleated mammalian cells via the Kennedy (CDP-choline) pathway in which CTP:phosphocholine cytidylyltransferase (CT) catalyzes the regulated and rate-limiting step (1Vance D.E. Biochem. Cell Biol. 1990; 68: 1151-1165Crossref PubMed Scopus (147) Google Scholar, 2Johnson J.E. Cornell R.B. Mol. Membr. Biol. 1999; 16: 217-235Crossref PubMed Scopus (240) Google Scholar, 3Lykidis A. Jackson P. Jackowski S. Biochemistry. 2001; 40: 494-503Crossref PubMed Scopus (41) Google Scholar). Two genes (Pcyta1 and Pcytb1, for CTα and CTβ, respectively) encode CT activity (4Lykidis A. Murti K.G. Jackowski S. J. Biol. Chem. 1998; 273: 14022-14029Abstract Full Text Full Text PDF PubMed Scopus (113) Google Scholar, 5Lykidis A. Baburina I. Jackowski S. J. Biol. Chem. 1999; 274: 26992-27001Abstract Full Text Full Text PDF PubMed Scopus (133) Google Scholar, 6Tang W. Keesler G.A. Tabas I. J. Biol. Chem. 1997; 272: 13146-13151Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar, 7Kalmar G.B. Kay R.J. Lachance A. Aebersold R. Cornell R.B. Proc. Natl. AcaSci. U. S. A. 1990; 87: 6029-6033Crossref PubMed Scopus (129) Google Scholar, 8Feldman D.A. Weinhold P.A. J. Biol. Chem. 1987; 262: 9075-9081Abstract Full Text PDF PubMed Google Scholar). CTα is ubiquitously expressed in nucleated cells (9Wang Y. Kent C. J. Biol. Chem. 1995; 270: 18948-18952Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar), and its expression is tightly regulated. CTα is also regulated post-translationally by reversible association with membrane lipids, which are required for its activity (10Tronchere H. Record M. Terce F. Chap H. Biochim. Biophys. Acta. 1994; 1212: 137-151Crossref PubMed Scopus (98) Google Scholar, 11Cornell R.B. Biochem. Soc. Trans. 1998; 26: 539-544Crossref PubMed Scopus (27) Google Scholar, 12Kent C. Biochim. Biophys. Acta. 1997; 1348: 79-90Crossref PubMed Scopus (190) Google Scholar, 13Pelech S.L. Cook H.W. Paddon H.B. Vance D.E. Biochim. Biophys. Acta. 1984; 795: 433-440Crossref PubMed Scopus (77) Google Scholar, 14Pelech S.L. Pritchard P.H. Brindley D.N. Vance D.E. J. Biol. Chem. 1983; 258: 6782-6788Abstract Full Text PDF PubMed Google Scholar). At the level of gene expression, CTα mRNA has been shown to increase after growth factor stimulation (15Tessner T.G. Rock C.O. Kalmar G.B. Cornell R.B. Jackowski S. J. Biol. Chem. 1991; 266: 16261-16264Abstract Full Text PDF PubMed Google Scholar), during liver development (16Sesca E. Perletti G.P. Binasco V. Chiara M. Tessitore L. Biochem. Biophys. Res. Commun. 1996; 229: 158-162Crossref PubMed Scopus (29) Google Scholar), in proliferating liver tissue following partial hepatectomy (17Houweling M. Cui Z. Tessitore L. Vance D.E. Biochim. Biophys. Acta. 1997; 1346: 1-9Crossref PubMed Scopus (56) Google Scholar), and during the S phase of the cell cycle (18Golfman L.S. Bakovic M. Vance D.E. J. Biol. Chem. 2001; 276: 43688-43692Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar). We recently reported that the expression of CTα is activated in late G1-S phase by the action of Sp1 (19Banchio C. Schang L.M. Vance D.E. J. Biol. Chem. 2003; 278: 32457-32464Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar) and repressed in quiescent cells by the action of histone deacetylase (20Banchio C. Lingrell S. Vance D.E. J. Biol. Chem. 2006; 281: 10010-10015Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar). The retinoblastoma gene product (Rb) was the first tumor suppressor to be identified (21Friend S.H. Bernards R. Rogelj S. Weinberg R.A. Rapaport J.M. Albert D.M. Dryja T.P. Nature. 1986; 323: 643-646Crossref PubMed Scopus (2220) Google Scholar). Rb regulates the expression of several genes through cis-acting elements in a cell type-dependent manner through the retinoblastoma control element (RCE), which is present in some genes responsible for cell growth and differentiation (22Mulligan G. Jacks T. Trends Genet. 1998; 14: 223-229Abstract Full Text Full Text PDF PubMed Scopus (279) Google Scholar). This element can be positively or negatively regulated by Rb and by three nuclear proteins of 115, 95, and 80 kDa (retinoblastoma control proteins (RCPs)) that bind RCE in vitro (23Kim S.J. Onwuta U.S. Lee Y.I. Li R. Botchan M.R. Robbins P.D. Mol. Cell. Biol. 1992; 12: 2455-2463Crossref PubMed Scopus (224) Google Scholar, 24Robbins P.D. Horowitz J.M. Mulligan R.C. Nature. 1990; 346: 668-671Crossref PubMed Scopus (223) Google Scholar, 25Creagh S.C. Robbins J.M. Littlejohn R.G. Physical Rev. A. 1990; 42: 1907-1922Crossref PubMed Scopus (120) Google Scholar, 26Udvadia A.J. Rogers K.T. Horowitz J.M. Cell Growth & Differ. 1992; 3: 597-608PubMed Google Scholar). The RCPs bind to the RCEs within the c-fos, c-myc, and transforming growth factor-β1 promoters (26Udvadia A.J. Rogers K.T. Horowitz J.M. Cell Growth & Differ. 1992; 3: 597-608PubMed Google Scholar). RCPs were shown to be members of the Sp1 transcription factor family. The 115- and 95-kDa RCP proteins correspond to Sp1 and Sp3 transcription factors, respectively, and activate RCE-mediated transcription. In contrast, the 80-kDa RCP, which is produced by internal initiation of transcription from Sp1 mRNA, acts as a potent inhibitor of Sp1/Sp3-mediated transcription (26Udvadia A.J. Rogers K.T. Horowitz J.M. Cell Growth & Differ. 1992; 3: 597-608PubMed Google Scholar, 27Udvadia A.J. Rogers K.T. Higgins P.D. Murata Y. Martin K.H. Humphrey P.A. Horowitz J.M. Proc. Natl. Acad. Sci. U. S. A. 1993; 90: 3265-3269Crossref PubMed Scopus (187) Google Scholar, 28Kennett S.B. Udvadia A.J. Horowitz J.M. Nucleic Acids Res. 1997; 25: 3110-3117Crossref PubMed Scopus (233) Google Scholar, 29Udvadia A.J. Templeton D.J. Horowitz J.M. Proc. Natl. Acad. Sci. U. S. A. 1995; 92: PubMed Scopus Google Scholar). transcription is by Rb protein (23Kim S.J. Onwuta U.S. Lee Y.I. Li R. Botchan M.R. Robbins P.D. Mol. Cell. Biol. 1992; 12: 2455-2463Crossref PubMed Scopus (224) Google Scholar). that Rb regulates transcription by with RCPs by binding to the RCE we two RCEs in the promoter of the We the of these RCEs and in CTα regulation in which the for and the were from and fetal bovine and fetal were from and were from were from Cell and cells were in with and fetal bovine in a at cells were in with fetal at were in by in with for and by of fetal bovine with CTα that alter transcription factor and were a Biol. 2001; PubMed Scopus Google Scholar). the was as M. W. Tabas I. Vance D.E. Biochim. Biophys. Acta. 1999; PubMed Scopus Google Scholar). Mutations in each of the sites were of as a control for and were the as by the and were activity was to expression of Rb was from L. Schang of and expression of Sp1 protein were from R. and A.J. R. Cell. Full Text PDF PubMed Scopus Google Scholar, S. R. Cell. 1990; Full Text PDF PubMed Scopus Google Scholar). and nuclear of cells to different of the cell cycle were as by and Nucleic Acids Res. 1991; PubMed Scopus Google Scholar). the RCE and Sp1 and and or in the RCE and and were by the of of were at for and to of was and each binding of of binding of nuclear and were for at after of the with nuclear of for Rb and Sp1 was for were by the of of The was on a and by of the were for in fetal bovine for cells were with for at were and three for each at with from and as by the and were from we used the following of and was of and of each for at for for and for the with we used a of and to the CTα promoter but not the CT were in of A. The cells were for at Cell were at for to and of were used for CT activity protein were the protein with bovine as a CT activity in the was in the of by the of to as S.L. Pritchard P.H. Vance D.E. J. Biol. Chem. Full Text PDF PubMed Google Scholar). each of CT; and for S. C. Mol. Google were by of each and of and a control were for each was the and the were for for by of for for and for of a was on the to CT were used to expression the and control CTα Two regulates transcription of the c-fos, c-myc, and transforming growth promoters through the RCE in in a or manner depending cell (26Udvadia A.J. Rogers K.T. Horowitz J.M. Cell Growth & Differ. 1992; 3: 597-608PubMed Google Scholar). of the CTα proximal promoter has that for Rb which are present in the promoter of a of growth factor genes (26Udvadia A.J. Rogers K.T. Horowitz J.M. Cell Growth & Differ. 1992; 3: 597-608PubMed Google Scholar). and are respectively, in and to the transcriptional and are shown in and these RCEs are to identified in the and Mutations the RCEs CTα the of these RCEs in CTα expression we two in which the CTα proximal promoter M. W. Tabas I. Vance D.E. Biochim. Biophys. Acta. 1999; PubMed Scopus Google that alter each of the RCE elements was to and the was to We these and were with each of these as a control. cells were by and were at both and S after cell cycle of the cell cycle. and were The shown in that each of the RCE binding sites is essential to CTα transcription. in activity was with both of the at both the and S of the cell cycle. Rb CTα but CTα from with in or the of Rb in the regulation of CTα expression, we each of the constructs with a to Rb or and as a control. Rb was the Rb mRNA was in cells and in We and in from cells that been in or in cells to S The by that Rb is involved in CTα expression in different depending on the phase of the cell cycle. In quiescent cells Rb CTα expression, but during the S phase Rb repressed CTα of the RCE elements was these two were abolished that the activity of the promoter a as demonstrated and that RCE elements are involved in the level of CTα transcription and that the regulation by Rb RCE the of the of Rb on CTα we CT activity in the Rb was during CT activity was by increase was not by the activity of the we not in CT activity after Rb during S phase The be by the of these In the in CTα mRNA as was not in activity to the CT activity in We not to Rb in cell be to alter cell cycle M. R. M. Kay E. Mol. 2006; 14: PubMed Scopus Google Scholar). Rb of CTα Sp1 (26Udvadia A.J. Rogers K.T. Horowitz J.M. Cell Growth & Differ. 1992; 3: 597-608PubMed Google Scholar, 27Udvadia A.J. Rogers K.T. Higgins P.D. Murata Y. Martin K.H. Humphrey P.A. Horowitz J.M. Proc. Natl. Acad. Sci. U. S. A. 1993; 90: 3265-3269Crossref PubMed Scopus (187) Google Scholar) demonstrated that of the that to the RCE elements is a of the Sp1 family. In we identified Sp1 as of CTα expression during the cell cycle. We that Sp1 to the Sp1 binding CTα expression when the cells S phase (19Banchio C. Schang L.M. Vance D.E. J. Biol. Chem. 2003; 278: 32457-32464Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar, C. Schang L.M. Vance D.E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus (45) Google Scholar). in quiescent cells the deacetylase CTα expression (20Banchio C. Lingrell S. Vance D.E. J. Biol. Chem. 2006; 281: 10010-10015Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar). In the Sp1 to Sp1 binding that was identified as a of CTα expression (19Banchio C. Schang L.M. Vance D.E. J. Biol. Chem. 2003; 278: 32457-32464Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar). both RCE sites are to Sp1 binding sites we the of Rb on CTα expression when Sp1 binding or was We cells with the constructs or or Rb was by not a with in the Sp1 was we increase of activity in both and S of the cell as was (19Banchio C. Schang L.M. Vance D.E. J. Biol. Chem. 2003; 278: 32457-32464Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar). when Rb was in these the transcriptional activity to that in control cells Rb and that the of CTα expression by Rb in phase Sp1 binding C. In cells with CTα activity decreased with as for a of CTα (19Banchio C. Schang L.M. Vance D.E. J. Biol. Chem. 2003; 278: 32457-32464Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar, M. Vance D.E. J. Res. Full Text Full Text PDF PubMed Google Scholar). in cells that also expressed Rb, expression during S phase was that the level of CTα transcription was to that in cells with in S phase that Rb the of Sp1 binding to Sp1 binding at least during the S or alters the that Sp1 through the Sp1 binding during the Sp1 CTα and by the Rb that both Sp1 and Rb CTα expression, we the of each factor by CTα expression in cells of these We cells and cells that not Sp1 A.J. R. Cell. Full Text PDF PubMed Scopus Google Scholar) and Rb J. A. H. J. PubMed Scopus Google Scholar), cell was with the after we and CTα mRNA and CTα the of CTα transcription by in cells was and was not or by of Rb or Sp1 We CTα mRNA expression by quantitative and CT activity but not changes after Rb Sp1 in these cells and In cells the transcriptional activity was in the of Sp1 as for a of CTα expression (19Banchio C. Schang L.M. Vance D.E. J. Biol. Chem. 2003; 278: 32457-32464Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar, M. Vance D.E. J. Res. Full Text Full Text PDF PubMed Google Scholar). transcription of the was by of Sp1 and shown in stimulation of CTα transcription by Rb was of Sp1 with of Rb was when both Sp1 and Rb proteins were We also the stimulation of expression that we in the for CT activity and cell physiology. CT activity in cells Rb and Sp1 was in control cells is to that Rb and Sp1 expression in cells was by that Rb or regulates the of Sp1 to CTα expression in Sp1 and Rb in to the CTα association Rb and Sp1 and the CTα promoter was by chromatin from were by the of of the CTα promoter was in association with and in chromatin from these cells a control chromatin was with In these CTα promoter was Sp1 and Rb in to RCE and Sp1 demonstrate that Sp1 and Rb CTα Sp1 and Rb a with the Sp1 the we and and We two different the and elements the the and the elements were from cells to and S nuclear from and as a two a and were with the of the with the a the we two were that not be defined The of the two decreased when the was with the of only the decreased when the was with was nuclear from cells in S phase the was with the was and not when the was in the of with decreased the of the the was with was decreased after with with we a these demonstrate that Sp1 and Rb or bind and with RCE and Sp1 binding elements in of from nuclear that with Sp1 and RCE were nuclear from in S phase with RCE and element in the and or in the of Sp1 and or Rb and are The are of two with in of the RCE the binding of Sp1 Rb, we with the to alter and and to alter and shown in when from cells were with two were a and that were to with the the was in the of the of both decreased that of the was not alter The was after the was with from cells in phase was was after with or and the in of the in vitro we a were with in the or we with and The was by to only the DNA. In with the in vitro when was Rb not with the CTα promoter The association of Rb with the CTα promoter was not when the was of from S phase cells with each two and a and that were not by or and we not Rb association with these that at least the element is required for the association of Rb with the DNA. Rb of CTα through Rb gene has been as a tumor suppressor is or in of has been that Rb cell by as a of transcription (23Kim S.J. Onwuta U.S. Lee Y.I. Li R. Botchan M.R. Robbins P.D. Mol. Cell. Biol. 1992; 12: 2455-2463Crossref PubMed Scopus (224) Google Scholar, 24Robbins P.D. Horowitz J.M. Mulligan R.C. Nature. 1990; 346: 668-671Crossref PubMed Scopus (223) Google Scholar, E. P. R. M.R. Cell. 1990; Full Text PDF PubMed Scopus Google Scholar). In of the c-fos, c-myc, and transforming growth factor-β1 promoters that regulation by Rb to promoters were identified (23Kim S.J. Onwuta U.S. Lee Y.I. Li R. Botchan M.R. Robbins P.D. Mol. Cell. Biol. 1992; 12: 2455-2463Crossref PubMed Scopus (224) Google Scholar). promoter a RCE In report we demonstrate that Rb regulates CTα promoter transcription through two in the CTα proximal during cell growth the for PC and CTα expression is (19Banchio C. Schang L.M. Vance D.E. J. Biol. Chem. 2003; 278: 32457-32464Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar, C. Schang L.M. Vance D.E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus (45) Google Scholar), we the of the identified RCEs on CTα expression in cells and in cells We used constructs with in each of the RCEs. The that both RCEs are required for CTα of each of these sites markedly decreased CTα transcription in both of the cell cycle This to Rb the expression of each of the was with a to Rb, the expression of the not that the RCEs are required to promote CTα transcription. when a with RCEs was in the of Rb, two different were the Rb during S Rb CTα This by the of transcription or Rb can CTα expression in in different of the cell cycle. The be to the regulation of Rb by that is to during of the cell cycle R.A. 1992; 12: Google Scholar, S. Weinberg R.A. Trends Biochem. Sci. 1992; Full Text PDF PubMed Scopus Google Scholar, S. V. A. Weinberg R.A. Cell. 1992; Full Text PDF PubMed Scopus Google Scholar). of Rb alter the of Rb to with In a report we demonstrated that of a Rb and histone deacetylase CTα transcription in quiescent cells We that was to the CTα promoter by Sp1 and (20Banchio C. Lingrell S. Vance D.E. J. Biol. Chem. 2006; 281: 10010-10015Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar). to the of CTα expression by Rb be the of a Rb and deacetylase with and In Rb the deacetylase from the proteins CTα The during is to the binding of Sp1 to the Sp1 binding CTα C. Schang L.M. Vance D.E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus (45) Google Scholar). Sp1 has been as of the RCP proteins that bind to the RCE (23Kim S.J. Onwuta U.S. Lee Y.I. Li R. Botchan M.R. Robbins P.D. Mol. Cell. Biol. 1992; 12: 2455-2463Crossref PubMed Scopus (224) Google Scholar). the of and the Sp1 binding the binding of the to the The common RCE identified in several promoter elements is a of the Sp1 binding P.D. Horowitz J.M. Mulligan R.C. Nature. 1990; 346: 668-671Crossref PubMed Scopus (223) Google Scholar, Cell. 1990; Full Text PDF PubMed Scopus Google Scholar). or not Rb regulates Sp1 transcriptional activity from the binding or the Sp1 binding also Rb the of the Sp1 binding on the on CTα expression, we used constructs in the Sp1 binding sites and the Sp1 was Rb CTα expression, that Rb can also CTα transcription by mechanism also in the of Rb, the of Sp1 on CTα expression can be through the RCE we Rb and the activity of the with a Sp1 a level of expression of CTα was in the of Sp1 Rb CTα the mechanism responsible for is not Rb as a Sp1 that the binding of Sp1 to the RCE that bind RCEs also been shown to bind that Sp1 binding sites A.J. Rogers K.T. Higgins P.D. Murata Y. Martin K.H. Humphrey P.A. Horowitz J.M. Proc. Natl. Acad. Sci. U. S. A. 1993; 90: 3265-3269Crossref PubMed Scopus (187) Google Scholar). that RCEs and Sp1 binding elements to the CTα expression during the cell cycle. Rb Sp1 to CTα Sp1 and Rb was when CTα promoter activity was in cells that Rb or Sp1 CTα transcription in cells was with that in and cells and was not by of Rb or Sp1 the CTα was by quantitative This can be by the that these cells in the of expression of the S. V. A. Weinberg R.A. Cell. 1992; Full Text PDF PubMed Scopus Google Scholar). we and CTα expression during the S phase through Sp1 In CTα expression was in the of a (19Banchio C. Schang L.M. Vance D.E. J. Biol. Chem. 2003; 278: 32457-32464Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar, M. Vance D.E. J. Res. Full Text Full Text PDF PubMed Google Scholar), but was by of Sp1 the expression of CTα was when both Rb and Sp1 were overexpressed. Rb only a Rb and Sp1 with the that Rb is not by binding to and a transcription factor but is involved in transcriptional initiation of CTα in both a and is that Rb with Sp1 or with a that with these proteins with the CTα and to the of the Sp1 and the RCEs in the binding of Rb and we and with and RCE Rb and Sp1 with the CTα promoter as we demonstrated by in Moreover, by we identified two that Rb and Sp1 and and when we used the but with a RCE was two were but not We not changes after of the nuclear with that Rb not bind to when the is the cell was with the we only of the two with the This both Rb and Sp1 proteins The of that during phase the RCE elements a that Sp1 and S is with both and and Rb as was by the We Sp1 as of the Sp1 CTα expression during S phase (19Banchio C. Schang L.M. Vance D.E. J. Biol. Chem. 2003; 278: 32457-32464Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar, C. Schang L.M. Vance D.E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus (45) Google Scholar). Sp1 a with and C. Schang L.M. Vance D.E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus (45) Google Scholar) the Sp1 not be to the we used the RCE we two of the with the these not Rb and We by in in which Rb was to be with the CTα promoter when was Rb bind to the we that RCEs are required for Rb to bind to the as RCPs bind to the and the of Rb by the The mechanism for CTα transcriptional regulation is from a or We that CTα expression is regulated that the cell CTα at the during of the cell cycle. In to the of regulatory mechanism we CTα mRNA and CTα activity in cells Rb The level of CTα mRNA was during S phase with phase that the the as for the of the we were to that of Rb Sp1 the level of CTα increase in CTα activity was after Rb that with expression of CTα promoter in CTα activity was when CTα transcription was can be by the of these cell In of the of Rb expression on CTα transcription a CTα In we identified two RCE elements that Rb regulation of the CTα We in which Rb regulation by RCE elements is that genes regulated in a cell as c-fos, c-myc, and common regulatory The reported the first that Sp1 binding sites and RCEs or to transcriptional regulation of gene We and for on the and for with and

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